scholarly journals Detection of TP53 and PIK3CA Mutations in Circulating Tumor DNA Using Next-Generation Sequencing in the Screening Process for Early Breast Cancer Diagnosis

2019 ◽  
Vol 8 (8) ◽  
pp. 1183 ◽  
Author(s):  
Rodriguez ◽  
Córdoba ◽  
Aranda ◽  
Álvarez ◽  
Vicioso ◽  
...  

Circulating tumor DNA (ctDNA) has emerged as a non-invasive “liquid biopsy” for early breast cancer diagnosis. We evaluated the suitability of ctDNA analysis in the diagnosis of early breast cancer after mammography findings, comparing PIK3CA and TP53 mutations between tumor biopsies and pre-biopsy circulating DNA. Matched plasma and frozen fresh tissue biopsies from patients with Breast Imaging-Reporting and Data System (BIRADS) 4c/5 mammography findings and subsequent diagnosis of primary breast cancer were analyzed using NGS TruSeq Custom Amplicon Low Input Panel (Illumina) and plasma SafeSEQ (Sysmex Inostics). The same plasma and tumor mutations were observed in eight of 29 patients (27.6%) with four in TP53 and five in PIK3CA mutations. Sequencing analysis also revealed four additional ctDNA mutations (three in TP53 and one in PIK3CA) previously not identified in three patients tissue biopsy. One of these patients had mutations in both genes. Age, tumor grade and size, immunohistochemical (IHC) subtype, BIRADS category, and lymph node positivity were significantly associated with the detectability of these blood tumor-derived mutations. In conclusion, ctDNA analysis could be used in early breast cancer diagnosis, providing critical clinical information to improve patient diagnosis.

2015 ◽  
Vol 16 (1) ◽  
pp. 39-50 ◽  
Author(s):  
Adrien Saliou ◽  
François-Clément Bidard ◽  
Olivier Lantz ◽  
Marc-Henri Stern ◽  
Anne Vincent-Salomon ◽  
...  

2020 ◽  
Vol 31 ◽  
pp. S313
Author(s):  
S. Siddique ◽  
D.A. Khan ◽  
M. Aamir ◽  
J.S. Khan ◽  
N. Matloob ◽  
...  

2019 ◽  
pp. 1-16 ◽  
Author(s):  
Fernando Moreno ◽  
Javier Gayarre ◽  
Sara López-Tarruella ◽  
María del Monte-Millán ◽  
Antonio C. Picornell ◽  
...  

PURPOSE Genetic heterogeneity between primary tumors and their metastatic lesions has been documented in several breast cancer studies. However, the selection of therapy for patients with metastatic breast cancer and the search for biomarkers for targeted therapy are often based on findings from the primary tumor, mainly because of the difficulty of distant metastasis core biopsies. New methods for monitoring genomic changes in metastatic breast cancer are needed (ie, circulating tumor DNA [ctDNA] genomic analysis). The objectives of this study were to assess the concordance of genomic variants between primary and metastatic tumor tissues and the sensitivity of plasma ctDNA analysis to identify variants detected in tumor biopsies. PATIENTS AND METHODS Next-generation sequencing technology was used to assess the genomic mutation profile of a panel of 54 cancer genes in matched samples of primary tumor, metastatic tumor, and plasma from 40 patients with metastatic breast cancer. RESULTS Using Ion Torrent technology (ThermoFisher Scientific, Waltham, MA), we identified 110 variants that were common to the primary and metastatic tumors. ctDNA analysis had a sensitivity of 0.972 in detecting variants present in both primary and metastatic tissues. In addition, we identified 13 variants in metastatic tissue and ctDNA not present in primary tumor. CONCLUSION We identified genomic variants present in metastatic biopsies and plasma ctDNA that were not present in the primary tumor. Deep sequencing of plasma ctDNA detected most DNA variants previously identified in matched primary and metastatic tissues. ctDNA might aid in therapy selection and in the search for biomarkers for drug development in metastatic breast cancer.


2015 ◽  
Vol 7 (302) ◽  
pp. 302ra133-302ra133 ◽  
Author(s):  
Isaac Garcia-Murillas ◽  
Gaia Schiavon ◽  
Britta Weigelt ◽  
Charlotte Ng ◽  
Sarah Hrebien ◽  
...  

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